A Study of RoActemra/Actemra (Tocilizumab) in Combination With Methotrexate Versus RoActemra/Actemra Monotherapy in Patients With Rheumatoid Arthritis and an Inadequate Response to Methotrexate

Hoffmann-La Roche261 enrolled

Overview

This randomized, double-blind, parallel-group study will evaluate the efficacy and safety of RoActemra/Actemra (tocilizumab) in combination with methotrexate versus RoActemra/Actemra monotherapy in patients with rheumatoid arthritis and an inadequate response to methotrexate. All patients will receive RoActemra/Actemra 8 mg/kg intravenously (iv) every 4 weeks plus oral methotrexate for 16 weeks. Patients achieving low disease activity at Week 16 will be randomized to receive a further 12 weeks of RoActemra/Actemra treatment plus either methotrexate or placebo. Anticipated time on study treatment is 28 weeks.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

DOUBLE

Enrollment

261

Conditions

Rheumatoid Arthritis

Interventions

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

Inclusion Criteria: * Adult patients, \>/= 18 years of age * Active moderate to severe rheumatoid arthritis (DAS28 \>/= 3.2) at baseline * Currently receiving methotrexate for at least 12 weeks, at a stable oral dose of at least 15 mg/week for at least 6 weeks prior to treatment (Day 1) * Body weight \< 150 kg * Oral corticoids must have been at stable dose for at least 25 out of 28 days prior to baseline; maximum dose 10 mg/day Exclusion Criteria: * Pregnant or nursing women * Major surgery (including joint surgery) within 8 weeks prior to screening or planned major surgery within 6 months after baseline * Rheumatic autoimmune disease other than RA * Functional class IV as defined by the American College of Rheumatology (ACR) Classification of Functional Status in Rheumatoid Arthritis * Prior history of or current inflammatory joint disease other than RA * Treatment with a biologic agent at any time prior to baseline * Treatment with traditional DMARDs other than methotrexate within 1 month (for leflunomide 3 months) prior to baseline * Intraarticular or parenteral corticosteroids within 6 weeks prior to baseline * Previous treatment with RoActemra/Actemra * History of severe allergic or anaphylactic reactions to human, humanized, or murine monoclonal antibodies * Known active current or history of recurrent infection * History of or currently active primary or secondary immunodeficiency * Active tuberculosis requiring treatment within the previous 3 years * Positive for HIV infection

Locations (54)

Unnamed facility

Albacete, Albacete, Spain

Unnamed facility

Orihuela, Alicante, Spain

Unnamed facility

Torrevieja, Alicante, Spain

Unnamed facility

Villajoyosa, Alicante, Spain

Unnamed facility

Badajoz, Badajoz, Spain

Unnamed facility

Outcomes

Primary Outcomes

Change in Disease Activity Score Based on 28-Joint Count (DAS28) From Week 16 to Week 28

The DAS28 is a combined index for measuring disease activity in rheumatoid arthritis (RA). The index includes swollen (range 0-28) and tender (range 0-28) joint counts, acute phase response (erythrocyte sedimentation rate \[ESR\] in millimeters per hour \[mm/hr\]), and general health status (participant global assessment of disease activity using visual analog scale \[VAS\], range 1-100 mm). DAS28, which uses a 28-joint count, is derived from the original DAS, which includes a 44-swollen joint count. The DAS28 scale ranges from 0 to 10, where higher scores represent higher disease activity.

Time frame: Baseline, Week 16, and Week 28

Secondary Outcomes

Percentage of Participants With DAS28 Score Less Than (<) 2.6 at Week 28

The DAS28 is a combined index for measuring disease activity in RA. The index includes swollen (range 0-28) and tender (range 0-28) joint counts, acute phase response (ESR in mm/hr), and general health status (participant global assessment of disease activity using VAS, range 1-100 mm). DAS28, which uses a 28-joint count, is derived from the original DAS, which includes a 44-swollen joint count. The DAS28 scale ranges from 0 to 10, where higher scores indicate worsening. DAS28 \<2.6 equals (=) remission.

Time frame: Week 28

Percentage of Participants With Clinical Disease Activity Index (CDAI) <2.8 at Week 28

CDAI is the sum of tender and swollen joint count based on 28 joints and the participant and physician global disease assessment (VAS 0-10 centimeters \[cm\]). CDAI total score 0-76; higher scores = greater affect due to disease activity. CDAI \<2.8 = clinical remission.

Time frame: Week 28

Percentage of Participants With Simplified Disease Activity Index (SDAI) <3.3 at Week 28

SDAI is calculated by a simple numerical sum of tender and swollen joint count (based on a 28-joint assessment), participant and physician global assessment of disease activity (VAS 0-10 cm), and level of C-reactive protein in milligram per deciliter (mg/dL). SDAI total score 0-86; higher scores = greater affect due to disease activity. SDAI \<3.3 = clinical remission.

Time frame: 28 weeks

Change in the Health Assessment Questionnaire Disability Index (HAQ-DI) From Week 16 to Week 28

HAQ-DI: participant-reported assessment of ability to perform tasks in 8 categories of daily living activities: dress/groom; arise; eat; walk; reach; grip; hygiene; and common activities over past week. Each item scored on 4-point scale from 0 to 3: 0 = no difficulty; 1 = some difficulty; 2 = much difficulty; 3 = unable to do. Overall score was computed as the sum of domain scores and divided by the number of domains answered. Total possible score range 0-3 where 0 = least difficulty and 3 = extreme difficulty.